Pentoxifylline inhibits Ig kappa gene transcription and rearrangements in pre-B cells.
Pentoxifylline (PF) has been used in a wide variety of clinical situations; however, the molecular consequences of this drug are not well characterized. In this paper we assayed the effects of PF in two models of pre-B differentiation. In 70Z pre-B cells, transcriptional induction of rearranged Ig kappa-chain gene in response to LPS was suppressed by PF, without affecting the induction of Rel family proteins. In contrast, kappa induction by IFN-gamma was not suppressed by PF, indicating that the drug inhibited certain activation pathways. We also found that LPS-induced activation of germline kappa transcription and V kappa to J kappa recombination were inhibited by PF in the pre-B cell line 38B9. These observations suggest that PF may adversely affect B lymphopoiesis during chronic administration.
Wang
W
W
Rosenstiel Research Center, Department of Biology, Brandeis University, Waltham, MA 02254, USA.
Rath
S
S
Durdik
J M
JM
Sen
R
R
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D015322:Gene Rearrangement, B-Lymphocyte / Q000187:drug effects*; D005803:Genes, Immunoglobulin / Q000187:drug effects*; D007145:Immunoglobulin kappa-Chains / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D051379:Mice; D010431:Pentoxifylline / Q000494:pharmacology*; D013234:Stem Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects / Q000276:immunology*
D007145:Immunoglobulin kappa-Chains; D007166:Immunosuppressive Agents; D015847:Interleukin-4; D007371:Interferon-gamma; D010431:Pentoxifylline